Casein glycomacropeptide hydrolysates ameliorate hepatic insulin resistance of C57BL/6J mice challenged with high-fat diet

Hepatic insulin resistance plays a vital role in the development of type 2 diabetes. In the current study, the reduction effects of casein glycomacropeptide hydrolysates obtained with papain (GHP) on hepatic insulin resistance were investigated in high-fat diet (HFD)-fed C57BL/6J mice. Mice were fed with HFD for 8 weeks and then gavaged with GHP at doses of 100, 200 and 400 mg/kg body weight daily for another 8 weeks while continuing with HFD feeding. Results showed that GHP significantly decreased the levels of fasting blood glucose and serum insulin, and homeostasis model of insulin resistance index in HFD mice. The glucose tolerance and hepatic glycogen content were increased by GHP treatment in HFD mice. Besides, the hepatic steatosis and macrophages infiltration were ameliorated by GHP in HFD mice. Furthermore, GHP reduced the serine phosphorylation of IRS-1 and elevated Akt phosphorylation, which increased GSK313 phosphorylation in liver tissue of HFD mice. The decreased hepatic AMPK phosphorylation and increased hepatic MAPK phosphorylation induced by HFD were reversed by GHP, which contributed to the restoration of hepatic insulin sensitivity, reduction of hepatic steatosis and macrophage infiltration. Thus, GHP supplementation may be an alternative therapeutic approach against hepatic insulin resistance.